In-situ strain tuning in hBN-encapsulated graphene electronic devices

Using a simple setup to bend a flexible substrate, we demonstrate deterministic and reproducible in-situ strain tuning of graphene electronic devices. Central to this method is the full hBN encapsulation of graphene, which preserves the exceptional quality of pristine graphene for transport experiments. In addition, the on-substrate approach allows one to exploit strain effects in the full range of possible sample geometries and at the same time guarantees that changes in the gate capacitance remain negligible during the deformation process. We use Raman spectroscopy to spatially map the strain magnitude in devices with two different geometries and demonstrate the possibility to engineer a strain gradient, which is relevant for accessing the valley degree of freedom with pseudo-magnetic fields. Comparing the transport characteristics of a suspended device with those of an on-substrate device, we demonstrate that our new approach does not suffer from the ambiguities encountered in suspended devices

Reinforcement Learning Based Production Control of Semi-automated Manufacturing Systems

In an environment which is marked by an increasing speed of changes, industrial companies have to be able to quickly adapt to new market demands and innovative technologies. This leads to a need for continuous adaption of existing production systems and the optimization of their production control. To tackle this problem digitalization of production systems has become essential for new and existing systems. Digital twins based on simulations of real production systems allow the simplification of analysis processes and, thus, a better understanding of the systems, which leads to broad optimization possibilities. In parallel, machine learning methods can be integrated to process the numerical data and discover new production control strategies. In this work, these two methods are combined to derive a production control logic in a semi-automated production system based on the chaku-chaku principle. A reinforcement learning method is integrated into the digital twin to autonomously learn a superior production control logic for the distribution of tasks between the different workers on a production line. By analyzing the influence of different reward shaping and hyper-parameter optimization on the quality and stability of the results obtained, the use of a well-configured policy-based algorithm enables an efficient management of the workers and the deduction of an optimal production control logic for the production system. The algorithm manages to define a control logic that leads to an increase in productivity while having a stable task assignment so that a transfer to daily business is possible. The approach is validated in the digital twin of a real assembly line of an automotive supplier. The results obtained suggest a new approach to optimizing production control in production lines. Production control shall be centered directly on the workers’ routines and controlled by artificial intelligence infused with a global overview of the entire production system

Foresighted digital twin for situational agent selection in production control

As intelligent Data Acquisition and Analysis in Manufacturing nears its apex, a new era of Digital Twins is dawning. Foresighted Digital Twins enable short- to medium-term system behavior predictions to infer optimal production operation strategies. Creating up-to-the-minute Digital Twins requires both the availability of real-time data and its incorporation and serve as a stepping-stone into developing unprecedented forms of production control. Consequently, we regard a new concept of Digital Twins that includes foresight, thereby enabling situational selection of production control agents. One critical element for adequate system predictions is human behavior as it is neither rule-based nor deterministic, which we therefore model applying Reinforcement Learning. Owing to these ever-changing circumstances, rigid operation strategies crucially restrain reactions, as opposed to circumstantial control strategies that hence can outperform traditional approaches. Building on enhanced foresights we show the superiority of this approach and present strategies for improved situational agent selection

Continuous adaption through real data analysis turn simulation models into digital twins

Digital twins of production systems enable new forms of production control, flexibility and continuous improvement. While off-the-shelf software for discrete-event simulation permits the fast implementation of rough simulation models with sufficient accuracy for project-based analysis, they lack the precision and generality of a digital twin. This paper presents an approach to close the gap between model and reality by continuous and iterative updates enabled by connecting the simulation model to IT systems and smart data analysis. However, handling different databases requires a generative and flexible modelling approach as well as suitable algorithms for probability distribution estimation and control logic identification. The presented approach was validated at a real world example from the automotive industry where an average deviation of output to reality per week of 0.1% was achieved, proving the effectiveness of the approach

Optimal capital allocation in a hierarchical corporate structure

We consider capital allocation in a hierarchical corporate structure where stakeholders at two organizational levels (e.g., board members vs line managers) may have conflicting objectives, preferences, and beliefs about risk. Capital allocation is considered as the solution to an optimization problem whereby a quadratic deviation measure between individual losses (at both levels) and allocated capital amounts is minimized. Thus, this paper generalizes the framework of Dhaene et al. (2012), by allowing potentially diverging risk preferences in a hierarchical structure. An explicit unique solution to this optimization problem is given. In several examples, it is shown how the optimal capital allocation achieves a compromise between conflicting views of risk within the organization

Reduced skin homing by functional Treg in vitiligo

In human vitiligo, cutaneous depigmentation involves cytotoxic activity of autoreactive T cells. It was hypothesized that depigmentation can progress in the absence of regulatory T cells (Treg). The percentage of Treg among skin infiltrating T cells was evaluated by immunoenzymatic double staining for CD3 and FoxP3, revealing drastically reduced numbers of Treg in non-lesional, perilesional and lesional vitiligo skin. Assessment of the circulating Treg pool by FACS analysis of CD4, CD25, CD127 and FoxP3 expression, and mixed lymphocyte reactions in presence and absence of sorted Treg revealed no systemic drop in the abundance or activity of Treg in vitiligo patients. Expression of skin homing receptors CCR4, CCR5, CCR8 and CLA was comparable among circulating vitiligo and control Treg. Treg from either source were equally capable of migrating towards CCR4 ligand and skin homing chemokine CCL22, yet significantly reduced expression of CCL22 in vitiligo skin observed by immunohistochemistry may explain failure of circulating, functional Treg to home to the skin in vitiligo. The paucity of Treg in vitiligo skin is likely crucial for perpetual anti-melanocyte reactivity in progressive disease.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/78696/1/j.1755-148X.2010.00688.x.pd

Variant of TYR and Autoimmunity Susceptibility Loci in Generalized Vitiligo.

BACKGROUND Generalized vitiligo is an autoimmune disease characterized by melanocyte loss, which results in patchy depigmentation of skin and hair, and is associated with an elevated risk of other autoimmune diseases. METHODS To identify generalized vitiligo susceptibility loci, we conducted a genomewide association study. We genotyped 579,146 single-nucleotide polymorphisms (SNPs) in 1514 patients with generalized vitiligo who were of European-derived white (CEU) ancestry and compared the genotypes with publicly available control genotypes from 2813 CEU persons. We then tested 50 SNPs in two replication sets, one comprising 677 independent CEU patients and 1106 CEU controls and the other comprising 183 CEU simplex trios with generalized vitiligo and 332 CEU multiplex families. RESULTS We detected significant associations between generalized vitiligo and SNPs at several loci previously associated with other autoimmune diseases. These included genes encoding major-histocompatibility-complex class I molecules (P=9.05×10−23) and class II molecules (P=4.50×10−34), PTPN22 (P=1.31×10−7), LPP (P=1.01×10−11), IL2RA (P=2.78×10−9), UBASH3A (P=1.26×10−9), and C1QTNF6 (P=2.21×10−16). We also detected associations between generalized vitiligo and SNPs in two additional immune-related loci, RERE (P=7.07×10−15) and GZMB (P=3.44×10−8), and in a locus containing TYR (P=1.60×10−18), encoding tyrosinase. CONCLUSIONS We observed associations between generalized vitiligo and markers implicating multiple genes, some associated with other autoimmune diseases and one (TYR) that may mediate target-cell specificity and indicate a mutually exclusive relationship between susceptibility to vitiligo and susceptibility to melanoma

Common variants in FOXP1 are associated with generalized vitiligo

In a recent genome-wide association study of generalized vitiligo, we identified ten confirmed susceptibility loci. By testing additional loci that showed suggestive association in the genome-wide study, using two replication cohorts of European descent, we observed replicated association of generalized vitiligo with variants at 3p13 encompassing FOXP1 (rs17008723, combined P = 1.04 × 10−8) and with variants at 6q27 encompassing CCR6 (rs6902119, combined P = 3.94 × 10−7)

Comprehensive association analysis of candidate genes for generalized vitiligo supports XBP1, FOXP3, and TSLP

We previously carried out a genome-wide association study of generalized vitiligo (GV) in non-Hispanic whites, identifying 13 confirmed susceptibility loci. In this study, we re-analyzed the genome-wide data set (comprising 1,392 cases and 2,629 controls) to specifically test association of all 33 GV candidate genes that have previously been suggested for GV, followed by meta-analysis incorporating both current and previously published data. We detected association of three of the candidate genes tested: TSLP (rs764916, P3.0E-04, odds ratio (OR)1.60; meta-P for rs38069333.1E-03), XBP1 (rs6005863, P3.6E-04, OR1.17; meta-P for rs22695779.5E-09), and FOXP3 (rs11798415, P5.8E-04, OR1.19). Association of GV with CTLA4 (rs12992492, P5.9E-05, OR1.20; meta-P for rs2317751.0E-04) seems to be secondary to epidemiological association with other concomitant autoimmune diseases. Within the major histocompatibility complex (MHC), at 6p21.33, association with TAP1-PSMB8 (rs3819721, P5.2E-06) seems to derive from linkage disequilibrium with major primary signals in the MHC class I and class II regions

Genome-wide association studies of autoimmune vitiligo identify 23 new risk loci and highlight key pathways and regulatory variants

Vitiligo is an autoimmune disease in which depigmented skin results from the destruction of melanocytes1, with epidemiological association with other autoimmune diseases2. In previous linkage and genome-wide association studies (GWAS1 and GWAS2), we identified 27 vitiligo susceptibility loci in patients of European ancestry. We carried out a third GWAS (GWAS3) in European-ancestry subjects, with augmented GWAS1 and GWAS2 controls, genome-wide imputation, and meta-analysis of all three GWAS, followed by an independent replication. The combined analyses, with 4,680 cases and 39,586 controls, identified 23 new significantly associated loci and 7 suggestive loci. Most encode immune and apoptotic regulators, with some also associated with other autoimmune diseases, as well as several melanocyte regulators. Bioinformatic analyses indicate a predominance of causal regulatory variation, some of which corresponds to expression quantitative trait loci (eQTLs) at these loci. Together, the identified genes provide a framework for the genetic architecture and pathobiology of vitiligo, highlight relationships with other autoimmune diseases and melanoma, and offer potential targets for treatment